Earlier experimental studies concluded that changes in the density of vasa vasorum—small blood vessels penetrating the walls of and supplying nutrients to large blood vessels such as arteries and veins—are associated with pathogenesis, coronary artery disease, and atherosclerotic plaque progression, as well as unstable and ruptured atherosclerotic lesions that occur predominantly within the proximal third of coronary arteries. The inhibition of vasa vasorum neovascularization was concluded to reduce plaque size. It has been speculated that a higher spatial density of vasa vasorum may contribute to the increased propensity towards neovascularization upon exposure to atherosclerotic risk factors, and may thereby subsequently lead to intraplaque hemorrhage and rupture.
Acute coronary syndrome (ACS) resulting in unstable angina, myocardial infarction, or even sudden cardiac death most commonly results from the rupture or erosion of high risk atherosclerotic plaques and subsequent thrombosis and occlusion of the coronary artery. Patients presenting with ACS are most often clinically asymptomatic before the cardiac events occur and often have no obstructive narrowing of the coronary artery lumen at the location of the subsequent plaque rupture. Thus, there is a growing interest in developing methodologies for the clinical detection of the components of the vulnerable plaque.
The role of vasa vasorum in the pathogenesis and the complications of coronary artery disease continue to emerge. While vasa vasorum have been implicated in a number of diseases, including atherosclerosis, understanding their functional anatomy and specific role in these diseases has been limited by the small size of the vasa vasorum and difficulty in imaging them. Micro-computed-tomography (micro-CT) and histological methods have been used, in in-vitro studies, to demonstrate that there is a vasa vasorum proliferation prior to the development of an atherosclerotic lesion and may contribute to plaque rupture. The density of vasa vasorum is increased due to the angiogenesis. The newly created capillaries, being very fragile, can be easily ruptured therefore amplifying the chances of hemorrhage. Moreover, the plaques with high density of vasa vasorum are more prone to rupture and cause heart attacks and sudden death. Thus, there is growing interest to detect the presence of vasa vasorum in the vascular wall and in the atherosclerotic lesion (mainly in the coronary circulation) at an early stage of the development of the vascular defect. The identification of the vasa vasorum in the plaque, for example, may facilitate identification of plaque at high risk and dictate different local therapy. The appropriate studies would benefit from a technique that allows the detection of vasa vasorum in-vivo, which has not been demonstrated so far.
The existing methodologies are not necessarily suitable to accomplish this goal. While vasa vasorum neovascularization can be assessed with the use of three-dimensional (3D) micro-CT, there is a need in developing an in-vivo methodology for the investigation of vasa vasorum. For example, detection of vasa vasorum associated with vulnerable plaque has been attempted based on a micro-bubble approach that requires a special catheter and the experimental data for which is not available yet. Well known ultrasound methodologies based on Doppler effect, while allowing for observation of blood flow along the vessel, are not well suited for registering the flow in a transverse direction, perpendicular to the arterial wall. In addition, interventional selective coronary angiography and CT, as well as MRI angiography methods, are not capable of detecting very early lesions that do not narrow the lumen of the blood vessels under examination. Nowadays, multi-slice computed tomography (MSCT), cardiac MRI, intravascular ultrasound imaging (IVUS), or optical coherence tomography (OCT) are used to evaluate coronary artery wall pathology. However, the IVUS and OCT methods, while providing important information about changes in the arterial wall, have not been successful in quantifying the density of vasa vasorum in the arterial wall. Moreover, minimally invasive CT and MRI approaches have spatial resolutions that are insufficient to resolve the coronary arterial wall, let alone the early plaques that do not encroach on the arterial lumen.
Thus, micro-CT imaging is considered one of the gold standard methods for the in vitro detection and quantification of the 3D network of vasa vasorum. In view of the above-mentioned findings on vasa vasorum in application to early atherosclerosis, changes in the density of vasa vasorum (manifesting as an increase in CT value due to contrast agent uptake) in the region of early plaque formation may be an effective indicator detectable with CT, even though the individual vasa vasorum (which are less than 200 μm in diameter) cannot be resolved. Hence, there is a need for systems and methods for analyzing vasa vasorum in vivo in clinical settings.